Intrinsic subtype and response to neoadjuvant chemotherapy with carboplatin and docetaxel (TCb) in triple-negative breast cancer (TNBC)

Date

10 Oct 2016

Session

Poster display

Presenters

Isabel Echavarria Diaz-Guardamino

Citation

Annals of Oncology (2016) 27 (6): 43-67. 10.1093/annonc/mdw364

Authors

I. Echavarria Diaz-Guardamino1, S. Lopez-Tarruella2, J.A. García-Sáenz3, H. Gomez Moreno4, F. Moreno3, Y. Jerez2, H. Fuentes4, I. Marquez-Rodas2, M. Cebollero5, M. Del Monte-Millan2, A. Picornell2, T. Massarrah1, A. Barnadas6, A. Prat7, A. Ballesteros García8, R. Colomer Bosch9, B. Pelaez10, M. González-Rivera2, C.M. Perou11, M. Martin2

Author affiliations

  • 1 Medical Oncology, Hospital General Universitario Gregorio Marañon, 28007 - Madrid/ES
  • 2 Medical Oncology, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid/ES
  • 3 Medical Oncology, Hospital Clinico Universitario San Carlos, Madrid/ES
  • 4 Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas - INEN, Lima 34 - Lima/PE
  • 5 Pathology, Hospital General Universitario Gregorio Marañon, Madrid/ES
  • 6 Medical Oncology, Hospital de la Santa Creu i Sant Pau, 08026 - Barcelona/ES
  • 7 Medical Oncology, Vall d’Hebron Institute of Oncology (VHIO),, 08035 - Barcelona/ES
  • 8 Medical Oncology, Hospital Universitario de La Princesa, Madrid/ES
  • 9 Medical Oncology, Hospital Universitario de La Princesa, 28006 - Madrid/ES
  • 10 Medical Oncology, Hospital clinico de Valladolid, Valladolid/ES
  • 11 Department Of Genetics, Lineberger Comprehensive Cancer Center University of North Carolina, Chapel Hill/US
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Background

Triple-negative breast cancer (TNBC), while sensitive to chemotherapy, remains a challenge due to its differential response to treatment and poor prognosis. In a population of TNBC patients treated with NACT with docetaxel plus carboplatin (TCb), we evaluated the predictive value of the intrinsic subtype by PAM50.

Methods

Pathological response was defined by RCB (residual cancer burden) method, with pathological complete response (pCR) considered as lack of invasive tumor in breast plus axilla (ypT0/isypN0). Intrinsic subtype was determined by PAM50 gene expression assay using the nCounter platform (nanoString Technologies Inc; Seattle, USA). Association between RCB and subtypes was assessed on R software.

Results

121 consecutive patients received NACT with TCb in a prospective multicenter trial, 95 were available for the PAM50 analysis. Overall, the distribution of responses was: pCR 44%, class I 13%, class II 31%, and class III 14%. The majority of the tumors were basal-like (BL) (83%), followed by HER2E (13%), normal-like (3%) and luminal B (1%). A clear difference between the intrinsic subtypes with regard to RCB distribution was found (p = 0.009, Table 1). BL tumors had a significantly better response to TCb: 51 % achieved pCRvs 13% of non-BL tumors (p = 0.0055). Multivariate analyses including tumor size and nodal status confirmed the significance of intrinsic subtype for the prediction of response. Concordantly, resistance to TCb was more frequent in non-BL tumors (38% RCB-II, 31% RCB-III) as compared to BL (29 % and 10%).

RCB distribution across subtypes (Symmans et al, JCO 2007)

% All (n = 95) Basal-like (n = 79) Non-Basal (n = 16)
pCR 44.2 50.6 12.5
RCB I 11.6 10.1 18.8
RCB II 30.5 29.1 37.5
RCB III 13.7 10.1 31.2

Conclusions

TCb was shown to be an effective NACT regimen for TNBC with a pCR rate of 44%. Intrinsic subtype by PAM50 helps predict response to NACT with TCb, with BL TNBC associated with significant better outcomes as compared to non-BL TNBC (pCR rates of 51 % vs 13% respectively, p 0.0051), although better predictors of response are still needed.

Clinical trial identification

NCT01560663

Legal entity responsible for the study

Instituto de Investigacion Sanitaria Gregorio Marañon, Universidad Complutense, Madrid

Funding

This work was partially supported by the Ministry of Economy and Competitiveness ISCIII-FIS grants PI12/02684, and RD12/0036/0076, co-financed by ERDF (FEDER) Funds from the European Commission, “A way of making Europe”.

Disclosure

All authors have declared no conflicts of interest.

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